Helicase antigen (HAGE)-derived vaccines induce immunity to HAGE and ImmunoBody®-HAGE DNA vaccine delays the growth and metastasis of HAGE-expressing tumors in vivo

Abstract

The management of patients with triple-negative breast cancer (TNBC) continues to pose a significant clinical challenge. Less than 30% of women with metastatic TNBC survive 5 years, despite adjuvant chemotherapy and the initial higher rates of clinical response that can be achieved with neoadjuvant chemotherapy. ImmunoBody is a plasmid DNA designed to encode a human antibody molecule with complementarity-determining regions engineered to express cytotoxic and helper T-cell epitopes derived from the cancer antigen of interest. The helicase antigen (HAGE) is a cancer testis antigen, which is expressed in TNBC. Herein, we have identified a 30-amino-acid-long HAGE-derived sequence containing human leukocyte antigen (HLA)-A2- and HLA-DR1-restricted epitopes and demonstrated that the use of this sequence as a peptide (with CpG/incomplete Freund's adjuvant) or incorporated into an ImmunoBody vaccine can generate specific interferon-γ-secreting splenocytes in HHDII⁺ DR1⁺ mice. T-cell responses elicited by the ImmunoBody-HAGE vaccine were superior to peptide immunization. Moreover, splenocytes from ImmunoBody-HAGE-vaccinated mice stimulated in vitro could recognize HAGE⁺ tumor cells and the human TNBC cell line MDA-MB-231. More importantly, the growth of implanted HHDII⁺ DR1⁺ HAGE⁺ Luc⁺ B16 cells.

Keywords: helicase antigen; metastasis; treatment; triple-negative breast cancer; vaccine.